This project has as its objective the exploration of metabolic processes leading to permanent hearing loss. It begins with the hypothesis that early stages of cochlear injury represent a disturbance of the microhomeostasis of the ear and may be reversible through treatment based on improved understanding of cochlear metabolism and pathophysiology. By a combination of biochemical, cytochemical and electrophysiological techniques we intend to determine biochemical mechanisms involved in the control of cochlear homeostasis and in disorders of this homeostasis caused by noise and ototoxic drugs. We are specifically interested in the role of adenylate cyclase in the regulation of ion and fluid balance and will determine influences of hormones and ototoxic drugs on its activity. We will also determine the influences of noise exposure on metabolic reactions that may lead to changes of cell membrane permeability and on glucose utilization in cochlear tissues.